C57BL/6-Tg(Aire-cre/Esr1)1Mmat/J

Stock number: 036499
Product name: Aire/CreER-BAC Tg
Research areas: Cancer Research, Immunology, Inflammation and Autoimmunity Research, Research Tools

Description

Aire/CreER mice carry a transgene which expresses tamoxifen-inducible cre recombinase under the direction of the mouse Aire promoter/enhancer elements, primarily in medullary thymic epithelial cells (mTECs). These mice may be useful in the study of immune self-tolerance and mTEC development.

Detailed description

The Aire gene encodes an E3 ubiquitin ligase which plays a critical role in immune self-tolerance induction, and exerts transcriptional control over a large number of tissue-restricted antigen (TRA) genes from medullary thymic epithelial cells (mTECs), where Aire is expressed most strongly.

The Aire/CreER transgenic allele (also called Aire/CreER BAC Tg) has a tamoxifen-inducible Cre recombinase inserted downstream of the Aire promoter/enhancer sequences. This is designed to have the Aire promoter/enhancer elements directing CreER expression primarily in mTECs within the thymus (see below), as well as to retain endogenous Aire expression. Specific details are below.

CreER fusion gene activity is inducible - observed following tamoxifen administration. As such, when Aire/CreER mice are bred with mice containing loxP-flanked sequences, tamoxifen-inducible Cre-mediated recombination will result in deletion of floxed sequences in Aire-expressing cells of the double mutant offspring.

The donating investigator reports that Aire/CreER mice have tamoxifen-inducible Cre recombinase activity that recapitulates the endogenous Aire expression pattern - observed mainly in medullary thymic epithelial cells (mTECs) of the thymus, with some expression in other cell types including peripheral B cells and some dendritic cells. The donating investigator reports no CreER activity (no reporter gene expression) is observed prior to tamoxifen exposure.

Mice hemizygous for the Aire/CreER transgene are viable and fertile with no reported gross physical or behavioral abnormalities. To date (September, 2021), it has not been attempted to make this strain homozygous.

In June 2022, genetic quality control screening and genotyping performed by The Jackson Laboratory on the first generation rederived colony identify the Aire/CreER transgene as having an inducible Cre that is recognized by our cre/Esr1 assay and not recognized by our cre/ERT2 assay.

The donating investigator has made several Aire mouse lines available: Aire-KO (Stock No. 036465), Aire/AGF-KI (Stock No. 036496), Aire/DTR-KI (Stock No. 036497), Aire/GFP-KI (Stock No. 036498), Aire/OVA-KI (Stock No. 036500), NOD 3xAire-KI (Stock No. 036558), B6 3xAire-KI (Stock No. 036693), Aire/CreER-BAC Tg (Stock No. 036499) and hAIRE-Tg (Stock No. 036559).

Development

The Aire/CreER transgenic allele (also called Aire/creER BAC Tg) was created in the laboratory of Dr. Mitsuru Matsumoto (Institute for Enzyme Research, Tokushima University). First, A bacterial artificial chromosome (BAC) transgenic construct containing 97.1 kb of the 59 region and 69 kb of the 39 region flanking the murine Aire gene was generated from BAC clone RP23-461E7, in which the Aire start codon was replaced with an open reading frame encoding a tamoxifen-inducible Cre recombinase followed by a poly-A signal from the rabbit β-globin gene. The construct was electroporated into the pronuclei of fertilized C57BL/6 oocytes and founders were chosen by Southern blot analysis. The resulting Aire/CreER colony was then interbred prior to sending embryos to The Jackson Laboratory Repository. Upon arrival, the strain was recovered and maintained by breeding mutant mice to wildtype mice from the colony or to C57BL/6J mice (Stock No. 000664).

In June 2022, genetic quality control screening and genotyping performed by The Jackson Laboratory on the first generation rederived colony identify the Aire/CreER transgene as having an inducible Cre that is recognized by our cre/Esr1 assay and not recognized by our cre/ERT2 assay.

Allele

Symbol: Tg(Aire-cre/Esr1)1Mmat
Name: transgene insertion 1, Mitsuru Matsumoto
MGI accession ID: MGI:5570119
Generation method: Transgenic
Attributes: Recombinase-expressing; Inducible
Synonyms: Aire/CreER BAC tg; Tg(Aire-cre/ERT2)1Mmat
Marker symbol: Tg(Aire-cre/Esr1)1Mmat
Marker name: transgene insertion 1, Mitsuru Matsumoto
Chromosome: UN
Strain of origin: C57BL/6
Molecular note: A targeting vector was constructed from a BAC (RP23-461E7) containing the entire Aire gene by replacing the Aire start codon with the open reading frame of a cre/Esr1 (originally reported as ERT2) fusion sequence and the polyA signal of rabbit beta-globin. The linearized BAC construct was microinjected into C57BL/6 fertilized pronuclei and founders were identified by Southern blot analysis. One line was established and crossed to reporter mouse lines for further analyses.